In recent years it has become quite evident that certain natural oligonucleotides exhibit growth regulatory function. Various oligonucleotides appear to regulate polymerases and initiate cellular differentiation. Such an oligonucleotide pppA2'p5'A2'p5'A has recently been discovered in interferon treated cells and appears to be responsible for inhibition of cellular proliferation by regulating cellular messenger RNA synthesis. This trimer is active at subnanomolar levels and is not degraded by the usual ribonucleases due to the 2',5'-phosphodiester linkage. The aim of the present proposal is to prepare such oligonucleotides, especially those containing a 2',5'-phosphodiester linkage and make such oligonucleotides available for antitumor evaluation in cell culture and in animal tumor model systems. It has been shown that certain oligonucleotides can enter tumor cells and it is hoped that such oligonucleotides will exert regulatory action which will control abnormal cellular proliferation characteristic of the cancer cell. Several different types of dinucleoside-2',5'-phosphate derivatives will be prepared and studied as inhibitors of DNA and RNA polymerase. Some monomeric derivatives such as formycin, tubercidin, toyocamycin and sangivamycin, which exhibit definite antitumor activity in animal systems, will also be studied as the 2',5'-linked oligomers with the hope that greater specificity of antitumor action might be obtained. Studies will be made of the synthesis and structure of certain oligonucleotide units structurally related to polyadenosine-diphosphate ribose (ADPR) which has been shown in eucaryotic cells to be obligatory for cell growth and division.